Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts usually present as soft, flesh-colored to brown plaques on the glans and shaft of the penis.
To provide an update on the current understanding, diagnosis and treatment of penile warts, a review was undertaken using key terms and phrases such as "penile warts" and "genital warts". The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies and reviews.
Epidemiology
HPV infection is the most common sexually transmitted disease worldwide. HPV infection does not mean that a person will develop genital warts. An estimated 0. 5 to 5% of sexually active young adult men have genital warts on physical examination. The peak age of the disease is 25 to 29 years.
Etiopathogenesis
HPV is a non-enveloped capsid double-stranded DNA virus, belonging to the genus Papillomavirus of the family Papillomaviridae and infects only humans. The virus has a circular genome 8 kilobases long, which encodes eight genes, including the genes for two encapsulating structural proteins, namely L1 and L2. The L1-containing virus-like particle is used in the production of HPV vaccines. L1 and L2 mediate HPV infection.
It is also possible to be infected with different types of HPV at the same time. In adults, genital HPV infection is transmitted primarily by sexual contact and, less commonly, by oral sex, skin-to-skin contact, and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, infection through close household contact and through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas in the skin or mucous membranes.
The incubation period for infection varies from 3 weeks to 8 months, with an average of 2 to 4 months. The disease is more common in individuals with the following predisposing factors: immunodeficiency, unprotected sexual intercourse, multiple sexual partners, sexual partner with multiple sexual partners, history of sexually transmitted infections, early sexual activity, shorter period of time between meeting a new partner and have sexual relations while living with him, not being circumcised and smoking. Other predisposing factors are humidity, maceration, trauma and epithelial defects in the penile region.
Histopathology
Histological examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distension, and large keratohyalin granules.
Clinical manifestations
Penile warts are usually asymptomatic and may occasionally be itchy or painful. Genital warts are usually located on the frenulum, the glans penis, the inner surface of the foreskin and the coronal sulcus. At the onset of the disease, penile warts usually appear as small, inconspicuous, soft, smooth, pearly, dome-shaped papules.
Lesions can occur individually or in groups (clustered). They can be pedunculated or broad-based (sessile). Over time, papules can turn into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungiform or cauliflower-shaped. The color may be flesh-colored, pink, erythematous, brown, violet, or hyperpigmented.
Diagnosis
The diagnosis is made clinically, usually based on history and physical examination. Dermoscopy and in vivo confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from finger- and pineal-shaped to mosaic. Among the characteristics of vascularization are glomerular, hooked and dotted vessels. Papillomatosis is an integral feature of warts. Some authors suggest using the acetic acid test (lightening of the surface of the warts when acetic acid is applied) to facilitate the diagnosis of penile warts.
The sensitivity of this test is high for hyperplastic penile warts, but for other types of penile warts and subclinical infected areas the sensitivity is considered low. Skin biopsy is rarely warranted, but should be considered in the presence of atypical features (e. g. , atypical pigmentation, induration, adhesion to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for warts refractory to several treatments. Although some authors propose PCR diagnosis to, among other things, determine the type of HPV that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
Differential diagnosis includes pearly penile papules, Fordyce granules, skin tags, condylomas lata in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, varicose capillary lymphangioma, lymphogranuloma venereum, scabies, syringoma, postneuroma. -traumatic, schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesThey appear as asymptomatic papules, small, smooth, soft, yellowish, pearly white or flesh-colored, conical or dome-shaped, with a diameter of 1 to 4 mm. Lesions are generally uniform in size and shape and symmetrically distributed. Typically, papules are located in single, double or multiple rows in a circle around the crown and groove of the glans penis. Papules tend to be more noticeable on the back of the crown and less noticeable towards the frenulum.
Fordyce granules- these are enlarged sebaceous glands. On the glans and shaft of the penis, Fordyce granules appear as smooth, asymptomatic, isolated or grouped, discrete, creamy-yellow papules with a diameter of 1 to 2 mm. These papules are most visible on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a dense, chalky, or cheese-like material can be extracted from these granules.
Acrochordons, also known as skintags ("skin tags"), are soft, skin-colored to dark brown, pedunculated or broad-based skin protuberances with a smooth contour. Sometimes they can be hyperkeratotic or warty in appearance. Most skin tags measure between 2 and 5 mm in diameter, although they can sometimes be larger, especially in the groin. Skin tags can appear almost anywhere on the body, but are most often seen on the neck and intertriginous areas. When they appear in the penile region, they can mimic penile warts.
Can condylomas- These are skin lesions in secondary syphilis caused by the spirochete Treponema pallidum. Clinically, condylomata lata appear as broad, moist, grayish-white, velvety, flat, or cauliflower-like papules or plaques. They tend to develop in warm, moist areas of the genitals and perineum. Secondary syphilis is characterized by a nonpruritic, diffuse, symmetric maculopapular rash on the trunk, palms, and soles. Systemic manifestations include headache, fatigue, pharyngitis, myalgia and arthralgia. Erythematous or whitish rashes on the oral mucosa may occur, as well as alopecia and generalized lymphadenopathy.
Annular granulomais a benign and self-limited inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, firm, brownish-purple, erythematous or skin-colored papules, generally arranged in a ring. As the condition progresses, central involution may be noted. A ring of papules often grows together to form a ring-shaped plaque. The granuloma is usually located on the extensor surfaces of the distal extremities, but can also be detected on the shaft and glans penis.
Lichen planus of the skinis a chronic inflammatory dermatosis that manifests as flat, polygonal, purple and itchy papules and plaques. Most often, the rash appears on the flexor surfaces of the hands, back, torso, legs, ankles and glans penis. Approximately 25% of lesions occur on the genitals.
Epidermal nevusis a hamartoma originating from the embryonic ectoderm that differentiates into keratinocytes, apocrine glands, eccrine glands, hair follicles and sebaceous glands. The classic lesion is a solitary, asymptomatic, well-circumscribed plaque that follows Blaschko's lines. The onset of the disease usually occurs in the first year of life. The color varies from pulp to yellow and brown. Over time, the lesion may thicken and become warty.
Capillary varicose lymphangioma is a benign saccular enlargement of the cutaneous and subcutaneous lymph nodes. The condition is characterized by clusters of bubbles resembling frog spawn. The color depends on the content: the whitish, yellow or light brown color is due to the color of the lymphatic fluid, and the reddish or bluish color is due to the presence of red blood cells in the lymphatic fluid as a result of hemorrhage. The blisters may change and acquire a warty appearance. More often found on the extremities, less often in the genital area.
Lymphogranuloma venereumis a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by a transient, painless genital papule and, less commonly, by an erosion, ulcer or pustule followed by inguinal and/or femoral lymphadenopathy known as buboes.
Generally,syringomasThey are asymptomatic papules, small, soft or dense, skin-colored or brown, measuring 1 to 3 mm in diameter. They are usually found in the periorbital areas and on the cheeks. However, syringomas can appear on the penis and buttocks. When located on the penis, syringomas can be confused with penile warts.
Schwanomas- These are neoplasms originating from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal surface of the penile shaft.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually appears as multiple reddish-brown papules or plaques in the anogenital area, mainly on the penis. The pathology is consistent with squamous cell carcinoma in situ. Progression to invasive squamous cell carcinoma occurs in 2 to 3% of cases.
Generally,squamous cell carcinomathe penis manifests itself in the form of a nodule, ulcer or erythematous lesion. The rash may appear warty, leukoplakia, or sclerosis. The most preferred location is the glans penis, followed by the foreskin and the shaft of the penis.
Complications
Penile warts can be a cause of significant concern or distress for the patient and their sexual partner due to their cosmetic appearance and contagiousness, stigmatization, concerns about future fertility and cancer risk, and their association with other sexually transmitted diseases. It is estimated that 20 to 34% of affected patients have underlying sexually transmitted diseases. Patients often experience feelings of guilt, shame, low self-esteem and fear. People with penile warts have higher rates of sexual dysfunction, depression, and anxiety compared to the healthy population. This condition can have a negative psychosocial impact on the patient and negatively affect their quality of life. Large exophytic lesions can bleed, cause urethral obstruction, and interfere with sexual intercourse. Malignant transformation is rare except in immunocompromised individuals. Patients with penile warts are at increased risk of developing anogenital cancer, head cancer, and neck cancer as a result of co-infection with high-risk HPV.
Forecast
If no treatment is given, genital warts may disappear on their own, remain unchanged, or increase in size and number. Approximately one-third of penile warts regress without treatment, and the average time until they disappear is approximately 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Although warts disappear, HPV infection may remain, leading to recurrence. Relapse rates range from 25 to 67% within 6 months of treatment. Among patients with subclinical infection, recurrent infection (reinfection) after sexual intercourse and in the presence of immunodeficiencies, a higher percentage of relapses occurs.
Treatment
Active treatment of penile warts is preferable to monitoring because it leads to faster resolution of lesions, reduces fear of infecting a partner, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relieves symptoms ( e. g. , itching, pain, or bleeding). Penile warts that persist for more than 2 years are much less likely to resolve on their own, so active treatment should be offered first. Counseling of sexual partners is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatments can be divided into mechanical, chemical, immunomodulatory and antiviral. There are very few detailed comparisons of different treatment methods with each other. Effectiveness varies depending on the treatment method. To date, no treatment has been proven to be consistently superior to other treatments. The choice of treatment should depend on the doctor's skill level, the patient's preference and tolerance to treatment, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of administration, side effects, cost and availability of treatment must also be taken into consideration. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient undergoes treatment at home (according to medical prescription)
Treatment methods used in the clinic
Methods used in the clinic include podophyllin, liquid nitrogen cryotherapy, bichloroacetic acid or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy.
Liquid podophyllin 25%, derived from podophyllotoxin, works by interrupting mitosis and causing tissue necrosis. The medicine is applied directly to the penile wart once a week for 6 weeks (maximum 0. 5 ml per treatment). Podophyllin should be washed off 1 to 4 hours after treatment and should not be applied to areas of high skin moisture. The effectiveness of wart removal reaches 62%. Due to reports of toxicity, including death, associated with the use of podofilin, podofilox, which has a much better safety profile, is considered preferred.
Liquid nitrogen, the preferred method for treating penile warts, can be applied using a spray bottle or cotton-tipped applicator directly to the wart and 2 mm around it. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form ice crystals. The minimum temperature required to destroy warts is -50°C, although some authors believe that -20°C is also effective.
The effectiveness of wart removal reaches 75%. Side effects include pain during treatment, erythema, peeling, blisters, erosion, ulceration and depigmentation at the application site. A recent phase II parallel randomized trial in 16 Iranian men with genital warts showed that cryotherapy using Wartner's formulation containing a mixture of 75% dimethyl ether and 25% propane was also effective. More research is needed to confirm or refute this conclusion. It must be said that cryotherapy with the Wartner composition is less effective than cryotherapy with liquid nitrogen.
Bichloroacetic acid and trichloroacetic acid can be used to treat small penile warts because their ability to penetrate the skin is limited. Each of these acids acts by coagulating proteins, followed by cell destruction and, consequently, removing the penile wart. A burning sensation may occur at the application site. Relapses after using bichloroacetic or trichloroacetic acid occur as often as with other methods. Medications can be used up to three times a week. Wart removal effectiveness ranges from 64 to 88%.
Electrocoagulation, laser therapy, carbon dioxide laser, or surgical excision work by mechanically destroying the wart and may be used in cases where there is a fairly large wart or a cluster of warts that is difficult to remove with treatment methods. conservatives. Mechanical treatment methods have a higher percentage of effectiveness, but their use presents a greater risk of scarring on the skin. Local anesthesia applied to non-occluded lesions 20 minutes before the procedure or a mixture of local anesthetics applied to occluded lesions one hour before the procedure should be considered measures that reduce discomfort and pain during the procedure. General anesthesia can be used to surgically remove large lesions.
Alternative Treatments
Patients who do not respond to first-line treatments may respond to other treatments or a combination of treatments. Second-line therapy includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Antiviral therapy with cidofovir may be considered for immunocompromised patients with treatment-refractory warts. Cidofovir is an acyclic nucleoside phosphonate that competitively inhibits viral DNA polymerase, thereby preventing viral replication.
Side effects of topical (intralesional) cidofovir include irritation, erosion, post-inflammatory pigmentary changes, and superficial scars at the application site. The main side effect of intravenous cidofovir is nephrotoxicity, which can be prevented with saline and probenecid hydration.
Prevention
Genital warts can be prevented to some extent by delaying sexual activity and limiting the number of sexual partners. Latex condoms, when used consistently and correctly, reduce the transmission of HPV. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective before sexual activity in primary prevention of infection. This is because vaccines do not offer protection against diseases caused by HPV vaccine types that an individual has acquired through previous sexual activity. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American Academy of Family Practice, and the International Human Papillomavirus Society recommend routine vaccination of girls and boys with the HPV vaccine.
The target age for vaccination is 11 to 12 years for girls and boys. The vaccine can be administered from 9 years of age. Three doses of the HPV vaccine should be administered in month 0, months 1 to 2 (usually 2), and months 6. Booster vaccination is indicated for men under 21 years of age and women under 26 years of age if have not been vaccinated at the expected age. Vaccination is also recommended for gay or immunocompetent men under the age of 26 if they have not been previously vaccinated. Vaccination reduces the likelihood of HPV infection and subsequent development of penile warts and penile cancer. Vaccinating both men and women is more beneficial in reducing the risk of genital warts on the penis than vaccinating only men, as men can acquire HPV infection from their sexual partners. The prevalence of anogenital warts decreased significantly from 2008 to 2014 due to the introduction of the HPV vaccine.
Conclusion
Penile warts are a sexually transmitted disease caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect their quality of life. Although approximately one-third of penile warts disappear without treatment, active treatment is preferred to hasten wart resolution, reduce fear of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated with penile lesions, and alleviate symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral, and are often combined. So far, no treatment has proven to be superior to others. The choice of treatment method should depend on the doctor's level of proficiency in this method, the patient's preference and tolerability of the treatment, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of use, side effects, cost and availability of the treatment must also be taken into consideration. HPV vaccines before sexual activity are effective in primary prevention of infection. The target age for vaccination is 11 to 12 years for girls and boys.